TY - JOUR
T1 - Efficient gene delivery into Epstein-Barr virus (EBV)-transformed human B cells mediated by replication-defective herpes simplex virus-1 (HSV-1)
T2 - A gene therapy model for EBV-related B cell malignancy
AU - Suzuki, Toshiya
AU - Piche, Alain
AU - Kasono, Keizo
AU - Xiang, Jialing
AU - Gomez-Navarro, Jesus
AU - Moriuchi, Shusuke
AU - Krisky, David M.
AU - Oligino, Thomas
AU - Glorioso, Joseph C.
AU - Curiel, Tyler J.
AU - Curiel, David T.
N1 - Funding Information:
We thank Connie H. Weldon for preparing the manuscript. Toshiya Suzuki is supported by the grant from Chugai Pharmaceutical Company, Japan. This work was supported by the following grants: Cure for Lymphoma Foundation; Leukemia Society of America; and National Cancer Institutes 5P30-CA1314A-25.
PY - 1998/11/27
Y1 - 1998/11/27
N2 - Subgroups of the B cell malignancies are known to be associated with Epstein-Barr virus (EBV) infection, especially in immunocompromised patients. These are fatal and refractory to conventional antineoplastic therapy. B cells are usually post-mitotic cells and even mitogen activated or transformed B cells have shown relative resistance against viral mediated gene transfer. To address this issue, we employed a replication-defective herpes simplex virus-1 (HSV-1) to mediate gene transfer into EBV-transformed B cells. The virus expresses the herpes simplex virus thymidine kinase (HSV-TK) and the E. coli lacZ reporter genes and is designated TOZ.1. We used the lymphoblastoid cell line SWEIG as a model for human EBV-related B cell malignancy. This cell line was established by in vitro EBV infection of primary human peripheral blood mononuclear cells. When SWEIG cells were infected with TOZ.1, X-gal staining revealed lacZ expression in more than 20% cells even at multiplicity of infection (MOI) as low as 1 and the expression persisted for at least one week. Ganciclovir (GCV) administration after TOZ.1 infection effectively decreased the number of the infected tumor cells in a dose-responsive manner. Viral toxicity was analyzed by cell proliferation assay (MTS assay) and found to be little even at 10 MOI infection. Three MOI of the virus yielded maximum antineoplastic effect and more than 50% tumor cells were killed by HSV-TK/GCV. These results suggest the potential utility of replication-defective HSV-1 for the treatment of EBV-related B cell malignancies.
AB - Subgroups of the B cell malignancies are known to be associated with Epstein-Barr virus (EBV) infection, especially in immunocompromised patients. These are fatal and refractory to conventional antineoplastic therapy. B cells are usually post-mitotic cells and even mitogen activated or transformed B cells have shown relative resistance against viral mediated gene transfer. To address this issue, we employed a replication-defective herpes simplex virus-1 (HSV-1) to mediate gene transfer into EBV-transformed B cells. The virus expresses the herpes simplex virus thymidine kinase (HSV-TK) and the E. coli lacZ reporter genes and is designated TOZ.1. We used the lymphoblastoid cell line SWEIG as a model for human EBV-related B cell malignancy. This cell line was established by in vitro EBV infection of primary human peripheral blood mononuclear cells. When SWEIG cells were infected with TOZ.1, X-gal staining revealed lacZ expression in more than 20% cells even at multiplicity of infection (MOI) as low as 1 and the expression persisted for at least one week. Ganciclovir (GCV) administration after TOZ.1 infection effectively decreased the number of the infected tumor cells in a dose-responsive manner. Viral toxicity was analyzed by cell proliferation assay (MTS assay) and found to be little even at 10 MOI infection. Three MOI of the virus yielded maximum antineoplastic effect and more than 50% tumor cells were killed by HSV-TK/GCV. These results suggest the potential utility of replication-defective HSV-1 for the treatment of EBV-related B cell malignancies.
UR - http://www.scopus.com/inward/record.url?scp=0032573358&partnerID=8YFLogxK
U2 - 10.1006/bbrc.1998.9685
DO - 10.1006/bbrc.1998.9685
M3 - Article
C2 - 9837767
AN - SCOPUS:0032573358
SN - 0006-291X
VL - 252
SP - 686
EP - 690
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -